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The Gut Microbiome in Hyperuricemia and Gout.
Arthritis Rheumatol
January 2025
Assistant Professor of Pathology and of Microbiology and Microbiology and Immunology, Stanford University, Stanford, CA, 94305.
Humans develop hyperuricemia via decreased urate elimination and excess urate production, consequently promoting monosodium urate crystal deposition and incident gout. Normally, approximately two thirds of urate elimination is renal. However, chronic kidney disease (CKD) and other causes of decreased renal urate elimination drive hyperuricemia in most with gout.
View Article and Find Full Text PDFMitochondrial segmentation and function prediction in live-cell images with deep learning.
Nat Commun
January 2025
Frontiers Science Center for Flexible Electronics, Xi'an Institute of Flexible Electronics (IFE) and Xi'an Institute of Biomedical Materials & Engineering, Northwestern Polytechnical University, Xi'an, China.
Mitochondrial morphology and function are intrinsically linked, indicating the opportunity to predict functions by analyzing morphological features in live-cell imaging. Herein, we introduce MoDL, a deep learning algorithm for mitochondrial image segmentation and function prediction. Trained on a dataset of 20,000 manually labeled mitochondria from super-resolution (SR) images, MoDL achieves superior segmentation accuracy, enabling comprehensive morphological analysis.
View Article and Find Full Text PDFProtein abundance of drug transporters and drug-metabolizing enzymes in paired healthy and tumor tissue from colorectal cancer patients.
Int J Pharm
January 2025
Drug Delivery and Disposition, KU Leuven, Gasthuisberg ON2, Herestraat 49 - box 921, 3000 Leuven, Belgium. Electronic address:
The widespread prevalence of colorectal cancer and its high mortality rate emphasize the urgent need for more effective therapies. When developing new drug products, a key aspect is ensuring that sufficiently high concentrations of the active drug are reached at the site of action. Drug transporters and drug-metabolizing enzymes can significantly influence the absorption and local accumulation of drugs in intestinal tissue.
View Article and Find Full Text PDFNavigating the Challenges of Cyclosporine as an Alternative to Rifampicin as an OATP1B Index Inhibitor.
Clin Pharmacol Ther
January 2025
Clinical Pharmacology, Pfizer R&D, Pfizer Inc, New York, New York, USA.
Rifampicin is a widely employed index inhibitor to assess the impact of organic anion transporting polypeptide 1B (OATP1B) inhibition on investigational drugs. The observation of nitrosamines in certain drug products, including rifampicin, has impacted the conduct of clinical drug-drug interaction (DDI) studies with rifampicin drug products. Cyclosporine is a recommended alternative to assess in vivo OATP1B activity; however, challenges exist in its use due to pharmacokinetic (PK) variability and non-selective inhibition of other drug disposition mechanisms.
View Article and Find Full Text PDFPopulation Pharmacokinetics of Sotorasib in Healthy Subjects and Advanced Solid Tumor Patients Harboring a KRAS Mutation from Phase 1 and Phase 2 Studies.
AAPS J
January 2025
Clinical Pharmacology Modeling and Simulation, Amgen, One Amgen Center Drive, Thousand Oaks, CA, 91320-0777, USA.
Sotorasib is a novel KRAS inhibitor that has shown robust efficacy, safety, and tolerability in patients with KRAS mutation. The objectives of the population pharmacokinetic (PK) analysis were to characterize sotorasib population PK in healthy subjects and patients with advanced solid tumors with KRAS mutation from 6 clinical studies, evaluate the effects of intrinsic and extrinsic factors on PK parameters, and perform simulations to further assess the impact of identified covariates on sotorasib exposures. A two-compartment disposition model with three transit compartments for absorption and time-dependent clearance and bioavailability well described sotorasib PK.
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